In-depth analysis of transcriptomes in ovarian cortical follicles from children and adults reveals interfollicular heterogeneity

Ilmatar Rooda (), Jasmin Hassan, Jie Hao, Magdalena Wagner, Elisabeth Moussaud-Lamodière, Kersti Jääger, Marjut Otala, Katri Knuus, Cecilia Lindskog, Kiriaki Papaikonomou, Sebastian Gidlöf, Cecilia Langenskiöld, Hartmut Vogt, Per Frisk, Johan Malmros, Timo Tuuri, Andres Salumets, Kirsi Jahnukainen, Agne Velthut-Meikas and Pauliina Damdimopoulou ()
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Ilmatar Rooda: Intervention and Technology, Karolinska Institutet, Huddinge
Jasmin Hassan: Intervention and Technology, Karolinska Institutet, Huddinge
Jie Hao: Intervention and Technology, Karolinska Institutet, Huddinge
Magdalena Wagner: Intervention and Technology, Karolinska Institutet, Huddinge
Elisabeth Moussaud-Lamodière: Intervention and Technology, Karolinska Institutet, Huddinge
Kersti Jääger: University of Tartu
Marjut Otala: Helsinki University Hospital, University of Helsinki
Katri Knuus: Helsinki University Hospital, University of Helsinki
Cecilia Lindskog: Uppsala University
Kiriaki Papaikonomou: Karolinska University Hospital
Sebastian Gidlöf: Intervention and Technology, Karolinska Institutet, Huddinge
Cecilia Langenskiöld: Sahlgrenska University Hospital
Hartmut Vogt: Linköping University
Per Frisk: Uppsala University Children’s Hospital
Johan Malmros: Karolinska University Hospital
Timo Tuuri: Helsinki University Hospital, University of Helsinki
Andres Salumets: Intervention and Technology, Karolinska Institutet, Huddinge
Kirsi Jahnukainen: University of Helsinki and Helsinki University Hospital
Agne Velthut-Meikas: Tallinn University of Technology
Pauliina Damdimopoulou: Intervention and Technology, Karolinska Institutet, Huddinge

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract The ovarian cortical reserve of follicles is vital for fertility. Some medical treatments are toxic to follicles, leading to premature ovarian insufficiency. Ovarian tissue cryopreservation is an established method to preserve fertility in adults and even applied in prepuberty despite unproven efficacy. Here, we analyze transcriptomes of 120 cortical follicles from children and adults for detailed comparison. We discover heterogeneity with two main types of follicles in both age groups: one with expected oocyte-granulosa profiles and another with predicted role in signaling. Transcriptional changes during growth to the secondary stage are similar overall in children and adults, but variations related to extracellular matrix, theca cells, and miRNA profiles are found. Notably, cyclophosphamide dose correlates with interferon signaling in child follicles. Additionally, morphology alone is insufficient for follicle categorization suggesting a need for additional markers. Marker genes for early follicle activation are determined. These findings will help refine follicular classification and fertility preservation techniques across critical ages.

Date: 2024
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DOI: 10.1038/s41467-024-51185-0

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